Untreated Adult Acute Lymphoblastic Leukemia
Current Clinical Trials
Standard treatment options for remission induction therapy:
Most current induction regimens for patients with adult acute lymphoblastic leukemia (ALL)
include prednisone, vincristine, and an anthracycline. Some regimens, including a Cancer and Leukemia Group B study (CALGB-8811), also add
other drugs, such as asparaginase or cyclophosphamide. Current multiagent
induction regimens result in complete response rates that range from 60% to
90%.[1-3]
Imatinib mesylate is often incorporated into the therapeutic plan for patients with Ph1-positive ALL. Several studies have suggested that the addition of imatinib results in complete response rates, event-free survival rates, and overall survival rates that are higher than those in historical controls. In each of these studies, common toxicities were nausea and liver enzyme abnormalities necessitating interruption and/or dose reduction of imatinib. (For more information on nausea, refer to the PDQ summary on Nausea and Vomiting.) Subsequent allogeneic transplant does not appear to be adversely affected by the addition of imatinib to the treatment regimen. At the present time, no conclusions can be drawn from these studies regarding which imatinib dose or schedule should be used.[4-6]
Two additional subtypes of adult ALL require special consideration. B-cell ALL [which
expresses surface immunoglobulin and cytogenetic abnormalities such as t(8;14),
t(2;8), and t(8;22)] is not usually cured with typical ALL regimens.
Aggressive brief duration high-intensity regimens, as evidenced in the Cancer and Leukemia Group B study (CALGB-9251), similar to those used in
aggressive non-Hodgkin lymphoma have shown high response rates and cure rates
(75% complete remission; 40% failure-free survival).[7,8] T-cell ALL,
including lymphoblastic lymphoma, similarly has shown high cure rates when
treated with cyclophosphamide-containing regimens.[3] Whenever possible, such
patients should be entered in clinical trials designed to improve the outcomes
in these subsets. (Refer to the B cell (Burkitt) lymphoma and T cell (lymphoblastic) lymphoma sections in the PDQ summary on Adult Non-Hodgkin Lymphoma
Treatment for more information.)
Since myelosuppression is an anticipated consequence of both the leukemia and
its treatment with chemotherapy, patients must be closely monitored during
remission induction treatment. Facilities must be available for hematological
support as well as for the treatment of infectious complications.
Supportive care during remission induction treatment should routinely include
red blood cell and platelet transfusions when appropriate.[9,10] Randomized
trials have shown similar outcomes for patients who received prophylactic
platelet transfusions at a level of 10,000/mm3 rather than
20,000/mm3.[11] The incidence of platelet alloimmunization was
similar among groups randomly assigned to receive pooled platelet concentrates
from random donors; filtered, pooled platelet concentrates from random donors;
ultraviolet B-irradiated, pooled platelet concentrates from random donors; or
filtered platelets obtained by apheresis from single random donors.[12]
Empiric broad spectrum antimicrobial therapy is an absolute necessity for
febrile patients who are profoundly neutropenic.[13,14] Careful instruction in
personal hygiene, dental care, and recognition of early signs of infection are
appropriate in all patients. Elaborate isolation facilities, including
filtered air, sterile food, and gut flora sterilization are not routinely
indicated but may benefit transplant patients.[15,16] Rapid marrow ablation
with consequent earlier marrow regeneration decreases morbidity and mortality.
White blood cell transfusions can be beneficial in selected patients with
aplastic marrow and serious infections that are not responding to
antibiotics.[17] Prophylactic oral antibiotics may be appropriate in patients
with expected prolonged, profound granulocytopenia (<100/mm3
for 2 weeks), though further studies are necessary.[18] To detect the
presence or acquisition of resistant organisms, serial surveillance cultures
may be helpful in such patients. As evidenced in a Cancer and Leukemia Group B study (CALGB-9111), the use of myeloid growth factors during
remission induction therapy appears to decrease the time to hematopoietic
reconstitution.[19,20]
Treatment options for remission induction therapy under clinical evaluation:
- Clinical trials are ongoing, and patients should be considered for these
studies.
Standard treatment options for central nervous system (CNS) prophylaxis:
The early institution of CNS prophylaxis is critical to achieve control of
sanctuary disease.
- Cranial radiation therapy plus intrathecal (IT) methotrexate.
- High-dose systemic methotrexate and IT methotrexate without cranial
therapy radiation.
- IT chemotherapy alone.
Current Clinical Trials
Check for U.S. clinical trials from NCI's PDQ Cancer Clinical Trials Registry that are now accepting patients with untreated adult acute lymphoblastic leukemia. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.
General information about clinical trials is also available from the NCI Web site.
References
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Hoelzer D, Thiel E, Löffler H, et al.: Prognostic factors in a multicenter study for treatment of acute lymphoblastic leukemia in adults. Blood 71 (1): 123-31, 1988.
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Linker CA, Levitt LJ, O'Donnell M, et al.: Treatment of adult acute lymphoblastic leukemia with intensive cyclical chemotherapy: a follow-up report. Blood 78 (11): 2814-22, 1991.
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Larson RA, Dodge RK, Burns CP, et al.: A five-drug remission induction regimen with intensive consolidation for adults with acute lymphoblastic leukemia: cancer and leukemia group B study 8811. Blood 85 (8): 2025-37, 1995.
[PUBMED Abstract]
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Thomas DA, Faderl S, Cortes J, et al.: Treatment of Philadelphia chromosome-positive acute lymphocytic leukemia with hyper-CVAD and imatinib mesylate. Blood 103 (12): 4396-407, 2004.
[PUBMED Abstract]
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Yanada M, Takeuchi J, Sugiura I, et al.: High complete remission rate and promising outcome by combination of imatinib and chemotherapy for newly diagnosed BCR-ABL-positive acute lymphoblastic leukemia: a phase II study by the Japan Adult Leukemia Study Group. J Clin Oncol 24 (3): 460-6, 2006.
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Wassmann B, Pfeifer H, Goekbuget N, et al.: Alternating versus concurrent schedules of imatinib and chemotherapy as front-line therapy for Philadelphia-positive acute lymphoblastic leukemia (Ph+ ALL). Blood 108 (5): 1469-77, 2006.
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Hoelzer D, Ludwig WD, Thiel E, et al.: Improved outcome in adult B-cell acute lymphoblastic leukemia. Blood 87 (2): 495-508, 1996.
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Lee EJ, Petroni GR, Schiffer CA, et al.: Brief-duration high-intensity chemotherapy for patients with small noncleaved-cell lymphoma or FAB L3 acute lymphocytic leukemia: results of cancer and leukemia group B study 9251. J Clin Oncol 19 (20): 4014-22, 2001.
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Slichter SJ: Controversies in platelet transfusion therapy. Annu Rev Med 31: 509-40, 1980.
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Murphy MF, Metcalfe P, Thomas H, et al.: Use of leucocyte-poor blood components and HLA-matched-platelet donors to prevent HLA alloimmunization. Br J Haematol 62 (3): 529-34, 1986.
[PUBMED Abstract]
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Rebulla P, Finazzi G, Marangoni F, et al.: The threshold for prophylactic platelet transfusions in adults with acute myeloid leukemia. Gruppo Italiano Malattie Ematologiche Maligne dell'Adulto. N Engl J Med 337 (26): 1870-5, 1997.
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Leukocyte reduction and ultraviolet B irradiation of platelets to prevent alloimmunization and refractoriness to platelet transfusions. The Trial to Reduce Alloimmunization to Platelets Study Group. N Engl J Med 337 (26): 1861-9, 1997.
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Hughes WT, Armstrong D, Bodey GP, et al.: From the Infectious Diseases Society of America. Guidelines for the use of antimicrobial agents in neutropenic patients with unexplained fever. J Infect Dis 161 (3): 381-96, 1990.
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Rubin M, Hathorn JW, Pizzo PA: Controversies in the management of febrile neutropenic cancer patients. Cancer Invest 6 (2): 167-84, 1988.
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Armstrong D: Symposium on infectious complications of neoplastic disease (Part II). Protected environments are discomforting and expensive and do not offer meaningful protection. Am J Med 76 (4): 685-9, 1984.
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Sherertz RJ, Belani A, Kramer BS, et al.: Impact of air filtration on nosocomial Aspergillus infections. Unique risk of bone marrow transplant recipients. Am J Med 83 (4): 709-18, 1987.
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Schiffer CA: Granulocyte transfusions: an overlooked therapeutic modality. Transfus Med Rev 4 (1): 2-7, 1990.
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Wade JC, Schimpff SC, Hargadon MT, et al.: A comparison of trimethoprim-sulfamethoxazole plus nystatin with gentamicin plus nystatin in the prevention of infections in acute leukemia. N Engl J Med 304 (18): 1057-62, 1981.
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Scherrer R, Geissler K, Kyrle PA, et al.: Granulocyte colony-stimulating factor (G-CSF) as an adjunct to induction chemotherapy of adult acute lymphoblastic leukemia (ALL). Ann Hematol 66 (6): 283-9, 1993.
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Larson RA, Dodge RK, Linker CA, et al.: A randomized controlled trial of filgrastim during remission induction and consolidation chemotherapy for adults with acute lymphoblastic leukemia: CALGB study 9111. Blood 92 (5): 1556-64, 1998.
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